Distinct CD4 T-cell effects on primary versus recall CD8 T-cell responses during viral encephalomyelitis.
Distinct CD4 T-cell effects on primary versus recall CD8 T-cell responses during viral encephalomyelitis.
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作者：
Hwang M;Phares TW;Hinton DR;Stohlman SA;Bergmann CC;Min B
CD4T细胞帮助并不是有效的原代CD8T细胞的普遍要求，但对于产生能够回忆反应的记忆CD8T细胞是必不可少的。这项研究考察了在亚致死性胶质萎缩冠状病毒诱导的脑脊髓炎期间，CD4T细胞如何影响中枢神经系统(CNS)内的初级和继发性抗病毒CD8T细胞反应。感染前CD4T细胞的耗尽不会损害病毒特异性CD8T细胞的外周扩张、干扰素-γ的产生、中枢神经系统的募集或初始的中枢神经系统效应能力。然而，在没有CD4T细胞的情况下，病毒控制受损与CNS CD8T细胞干扰素-γ的产生逐渐减少有关。此外，在CD8T细胞群体中，短期效应细胞增加，记忆前体效应细胞显著减少，这与更高的T细胞周转率一致。转移记忆CD8T细胞以降低CD4耗竭小鼠的病毒载量，使受体CNS CD8T细胞表型恢复到野生型对照小鼠。然而，与受助者相比，没有CD4T细胞的记忆CD8T细胞转移到受感染的CD4充足的接受者体内的扩增效率较低，并且不能在中枢神经系统中维持。这些数据表明，只要抗原暴露的时间有限，CD4T细胞对于初始扩增、CNS募集和初级常驻记忆CD8T细胞的分化是必不可少的。相比之下，CD4T细胞对于延长中枢神经系统中最初的CD8T细胞的功能和印记记忆CD8T细胞的回忆反应是必不可少的。
CD4 T-cell help is not a universal requirement for effective primary CD8 T cells but is essential to generate memory CD8 T cells capable of recall responses. This study examined how CD4 T cells affect primary and secondary anti-viral CD8 T-cell responses within the central nervous system (CNS) during encephalomyelitis induced by sublethal gliatropic coronavirus. CD4 T-cell depletion before infection did not impair peripheral expansion, interferon-γ production, CNS recruitment or initial CNS effector capacity of virus-specific CD8 T cells ex vivo. Nevertheless, impaired virus control in the absence of CD4 T cells was associated with gradually diminished CNS CD8 T-cell interferon-γ production. Furthermore, within the CD8 T-cell population short-lived effector cells were increased and memory precursor effector cells were significantly decreased, consistent with higher T-cell turnover. Transfer of memory CD8 T cells to reduce viral load in CD4-depleted mice reverted the recipient CNS CD8 T-cell phenotype to that in wild-type control mice. However, memory CD8 T cells primed without CD4 T cells and transferred into infected CD4-sufficient recipients expanded less efficiently and were not sustained in the CNS, contrasting with their helped counterparts. These data suggest that CD4 T cells are dispensable for initial expansion, CNS recruitment and differentiation of primary resident memory CD8 T cells as long as the duration of antigen exposure is limited. By contrast, CD4 T cells are essential to prolong primary CD8 T-cell function in the CNS and imprint memory CD8 T cells for recall responses.